Amicosante Massimo, Fontenot Andrew P
Department of Internal Medicine, University of Rome "Tor Vergata", Rome, Italy.
Clin Immunol. 2006 Nov;121(2):134-43. doi: 10.1016/j.clim.2006.03.012. Epub 2006 May 12.
Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by beryllium exposure in the workplace and is characterized by the accumulation of beryllium-specific CD4(+) T cells. Depending on genetic susceptibility and the nature of the exposure, CBD occurs in up to 20% of exposed workers. Genetic susceptibility has been associated with particular HLA-DP alleles, especially those possessing a negatively charged glutamic acid residue at the 69th position of the beta-chain. The mechanism for this association lies in the ability of these HLA-DP molecules to bind and present beryllium to pathogenic CD4(+) T cells. Large numbers of effector memory, beryllium-specific CD4(+) T cells are recruited to the lung of these subjects and secrete Th1-type cytokines upon beryllium recognition. The presence of circulating beryllium-specific CD4(+) T cells directly correlates with the severity of lymphocytic alveolitis. With the presence of a known antigenic stimulus, CBD serves as an important model of immune-mediated, organ destruction. Thus, our findings in CBD have important implications for studies in autoimmune diseases, in particular those with an unknown inciting antigen and an inaccessible target organ.
慢性铍病（CBD）是一种因工作场所接触铍而引起的肉芽肿性肺部疾病，其特征是铍特异性CD4(+) T细胞的积累。根据遗传易感性和接触性质，高达20%的接触工人会患上CBD。遗传易感性与特定的HLA-DP等位基因有关，特别是那些在β链第69位具有带负电荷谷氨酸残基的等位基因。这种关联的机制在于这些HLA-DP分子能够结合铍并将其呈递给致病性CD4(+) T细胞。大量效应记忆性铍特异性CD4(+) T细胞被招募到这些受试者的肺部，并在识别铍后分泌Th1型细胞因子。循环中铍特异性CD4(+) T细胞的存在与淋巴细胞性肺泡炎的严重程度直接相关。在已知抗原刺激存在的情况下，CBD是免疫介导的器官破坏的重要模型。因此，我们在CBD方面的发现对自身免疫性疾病的研究具有重要意义，特别是那些具有未知激发抗原和难以接近的靶器官的疾病。
